Suicide claims 1 million lives each year, and for each completed suicide, there are twenty suicide attempts, making it an important public health issue. Over 90% of suicide victims have at least one psychiatric diagnosis, including bipolar disorder (Mann, 2002), where as much as 8% of bipolar patients followed for up to 40 years died from suicide (1, 2).
Suicide has a prominent genetic component (reviewed in 3). Suicide attempts tend to occur more often within families (Johnson et al, 1998; Brent et al, 2002). Greater concordance was observed between monozygotic twins than between dizygotic twins (4, 5). The concordant phenotype includes both completed and attempted suicides (4). A review of twin studies estimated the heritability of suicidal behavior to be up to 55% (6).
A number of linkage studies have been conducted on suicide (7, 8). Their findings on the short arm of chromosome 2 were later replicated in 162 bipolar disorder families (9). Recent technological advances have permitted the high-throughput genotyping of hundreds of thousands of single-nucleotide polymorphisms across the genome. A number of suggestive findings have emerged (10, 11). Recently, a genome-wide association study (GWAS) was reported on samples of 2698 bipolar disorder patients of which 1201 had a previous suicide attempt. After meta-analysis of markers with p<1×10−3 from their discovery sample (GAIN, TGEN, German) with their replication bipolar disorder sample (STEP-BD, WTCCC, UCL), the most significantly associated marker was rs300774 in an intergenic region at chromosomal region 2p25, which contains the SH3YL1, ACP1, and FAM150B genes. The association finding was supported by post-mortem prefrontal cortical gene expression analysis, where suicide completers were found to have significantly higher ACP1 expression than non-suicide victims (12). The strongest association signal from another GWAS of suicide attempt on the bipolar disorder (STEP-BD, WTCCC, UCL) came from the intergenic chromosome 10 marker rs1466846; this finding was not replicated in the replication sample (GAIN, TGEN, German) (10). A GWAS on suicidality scores, which are derived from the SCAN interview, was conducted with a major depression sample from the RADIANT study (11). The suicidality score captures suicide severity from suicide ideation to attempt. The most significant findings from the RADIANT sample failed to replicate in the German replication sample.
At the present time, there is a lack of meaningful genetic predictors of suicidal behavior. Thus, there is a need in the art for diagnostic assays and tests to identify subjects at risk for suicide. Further there is a need in the art to genetic markers and kits that can be used to identify subjects at risk for suicide.